Sunnybrook Health Science Centre Research Articles

Outcomes of Patients with Acute Myeloid Leukemia with Myelodysplasia Related Changes (AML-MRC) Receiving Intensive Vs. Non-Intensive First Line Treatment

Background: Acute myeloid leukemia with myelodysplasia related changes (AML-MRC) a distinct clinico-pathologic subtype of AML recognized in the WHO and ICC 2022 classifications of hematolymphoid neoplasms (AML-MRC and AML-MR respectively). Compared to other subtypes, patients with AML-MRC/AML-MR have a worse prognosis and are less likely to respond to treatment. Traditionally, patients who are eligible for allogenic stem cell transplant (SCT) with AML-MRC/AML-MR are given high intensity chemotherapy (IC), such as daunorubicin and cytarabine (“7+3”), liposomal 7+3 or fludarabine+cytarabine+idarubicin (FLAG-IDA) whereas patients who are not transplant-eligible were treated with hypomethylating agents (i.e. azacitidine). Recently, azacitidine + venetoclax (aza/ven) has emerged as an important option for all AML patients over 75 years of age or with significant comorbidities who are not eligible for IC. However, the efficacy of aza/ven compared to IC for AML-MRC who are candidates for either has not been clearly established. Methodology: We conducted a single centre retrospective review of patients diagnosed with AML-MRC/AML-MR at Sunnybrook Health Science Centre (SHSC). A list of patients with AML-MRC/AML-MR was compiled from records from the Sunnybrook Hematology Biobank, which collects specimens and clinical data from 95% of acute leukemia patients presenting to SHSC. 65 patient charts were reviewed, and 60 patients were included in the study. 3 patients were not treated at SHSC and 2 were more appropriately classified as AML with recurrent genetic abnormalities. Treatment with a “7+3” backbone or FLAG-IDA were considered ‘intensive’ regimens; treatment with azacitidine with or without venetoclax, and low dose cytarabine (LDAC), with or without venetoclax were considered ‘non-intensive.‘ ELN 2022 criteria were used to evaluate responses to therapy. Results: 60 patients with AML-MRC/AML-MR were treated at SHSC from January 2021 to April 2023. The median age was 74 (37-99) y.o. 34 patients were male. The upper age of eligibility for allogeneic stem cell transplant was considered 72 years for this study. 28 patients were SCT eligible (31-72y.o.) and 32 patients were SCT ineligible (73-99y.o.). For SCT eligible patients, 14/28 were treated intensively and 10/28 were treated non intensively. 4 patients did not receive treatment. Of the SCT eligible group, 6/14 intensively treated patients achieved a CR/CRi compared to 5/10 non-intensively treated patients. For SCT ineligible patients, 8/32 did not receive treatment and the remaining 24 were treated non intensively. 12/24 SCT ineligible patients receiving treatment were given azacitidine+ venetoclax (aza/ven) and 9/12 achieved a CR/CRi. 7/24 patients received LDAC + venetoclax and 3/7 achieved a CR. In total, 14/60 patients were treated intensively, 21/60 patients were treated with aza/ven, 7/60 received LDAC+venetoclax, 5/60 azacitidine alone and 1/60 LDAC alone. 12/60 patients did not receive leukemia-directed therapy, either due to concomitant illness precluding treatment or a decision to decline treatment. Notably, 14/21 patients receiving aza/ven achieved a CR/CRi compared to 6/14 intensively treated patients, though more intensively treated patients ultimately proceeded to transplant (Figure 1). 48 patients who underwent therapy had next generation sequencing data for mutations of interest in AML. The most common mutations found in this cohort were ASXL1 (32), SRSF2 (20), RUNX1 (18), TET2 (17), IDH2 (16) and TP53 (12). No differences were found between patients that responded to first line therapy compared to those that did not, or those that responded to intensive chemotherapy compared to those responding to non-intensive treatment (Figure 2). Conclusion: Aza/Ven is an effective treatment regimen for AML-MRC/AML-MR, with 14/21 patients achieving CR/CRi after firstline treatment compared to 6/14 patients after IC. 4/4 patients achieved CR/CRi with salvage aza/ven after failing to respond to IC. Our study suggests that aza/ven should be considered as a firstline treatment option even in patients who are fit for intensive therapy as a means to achieve adequate responses to bridge to allogenic stem cell transplant without attendant toxicities associated with IC. Further studies are required to determine if specific mutations can predict response to either aza/ven or intensive treatment.

Functional decline and resilience in older adults over the age of 70 receiving radiotherapy for breast cancer: A pilot study

IntroductionRadiotherapy (RT) as an adjuvant, post-lumpectomy treatment has been shown to improve local control and survival in people with breast cancer. While adverse events because of cancer treatments are common, many older adults have demonstrated the ability to return to their baseline levels of physical functioning. There are limited reports on the functional decline and recovery of older patients undergoing RT. The primary objective of this study was to investigate physical function at various time points during RT in people with breast cancer over age 70 and their ability to recover post-decline. Materials and MethodsSeventy-nine patients with breast cancer aged 70+ undergoing adjuvant RT at Sunnybrook Health Science Centre, Toronto, Ontario, Canada were enrolled for a prospective observational study. Participants completed the EORTC QLQ-C30 quality of life questionnaire before their first RT, after their final RT, and at three- and six-months post-RT to assess changes in physical function. Descriptive statistics were utilized to evaluate EORTC QLQ-C30 scores. A higher score was indicative of poorer physical function. Physical decline was a 10+ point increase in EORTC QLQ-C30 score from baseline to the last RT, and resilience was a return to <10 points from the baseline score within six months post-RT. Resistance was a post-RT change from the baseline score by fewer than 10 points. ResultsNine patients (11%) experienced physical decline following their last RT, and two of them (22%) displayed resilience within six months. There were no demographic or symptom variables associated with functional decline from the baseline to post-RT, nor with resilience. Nausea, pain, and diarrhea post-RT were associated with functional decline at six months post-RT (P = 0.0185, P = 0.0449, P = 0.0007, respectively). Nausea and diarrhea at baseline were associated with resistance to decline (P = 0.0055, P = 0.019, respectively), and with decline at the six-month follow-up (P ≤0.0001, P = 0.0235, respectively). DiscussionThis study highlights the incidence of physical decline in patients over age 70 receiving RT for breast cancer and identifies risk factors for decline. Future research with a larger sample, longer follow-up period, and incorporating geriatric assessments pre-RT is warranted to better understand functional decline and resilience in this population.

Protocol for psychometric evaluation of the Amyotrophic Lateral Sclerosis - Bulbar Dysfunction Index (ALS-BDI): a prospective longitudinal study

IntroductionEarly detection and tracking of bulbar dysfunction in amyotrophic lateral sclerosis (ALS) are critical for directing management of the disease. Current clinical bulbar assessment tools are lacking, while existing physiological...

Cardiovascular Risk Factors in Women with History Hypertensive Disorder of Pregnancy Seen at Post Partum Maternal Health Clinic: A Retrospective Study

Cardiovascular disease is the leading cause of death in Canadian women. Women have unique risk factors for cardiovascular disease (CVD) including pregnancy complications such as hypertensive disorders of pregnancy, gestational diabetes, idiopathic preterm birth, and intrauterine growth restriction which impact close to 20% of women. Hypertensive Disorders of Pregnancy (HDP) were identified as risk factor for CVD in the 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Sunnybrook Health Science Centre implemented an inter-professional post-partum maternal health clinic (4P Maternal Health Clinic) in 2014 for women whose pregnancy was complicated by a HDP.

P022: Geriatrics care in the ED: Acute care use after the introduction of an interdisciplinary care program in Sunnybrook Health Sciences Centre's Emergency Department

Introduction: Currently the top 5% of complex patients consume 84% of Ontario’s Hospital and Home Care costs. There is a critical need for a dynamic, person-centred care planning process for medically complex patients with real time dialogue between ED/acute care and community care providers at care transitions. A care pathway was developed in the Sunnybrook Health Science Centre’s Emergency Department using quality improvement methodology and team. The purpose of this study is to evaluate the impact of the emergency room huddle for complex care patients on emergency doctors’ perceptions of patient safety and ED efficiency measures such as department flow and delays. Methods: Intervention - Medically complex patients with frequent ED use are now automatically flagged upon registration in the Emergency Department (ED) and an ED Care Coordination team is notified by secure email: GEM nurse, ED CCAC Care Coordinator, SW, OT/PT. The GEM nurse initiates a comprehensive patient assessment in the Emergency Department right after triage and the CCAC Care Coordinator initiates a teleconference with the patient’s family physician and community Care Coordinator with the patient’s consent. Usual physician assessment is preceded and followed by an inter-professional huddle (including the EM doctor, GEM nurse, CCAC nurse and SW, OT, PT) to ensure patient's needs, goals and team recommendations are clear. Emergency doctors who have participated in an inter-professional huddle for complex care patients are contacted via a semi-structured interview and Qualtrics surveys evaluating perceptions of patient safety and ED efficiency measures such as department flow and delays. Results: Qualitative analysis of the results will be conducted and results updated at a later date. Conclusion: Safety is enhanced through better communication between ED providers, patients, their family physicians and community care providers. It is essential that the inter-professional huddle is recognized by emergency physicians as an important element of patient safety and care. An evaluation of ED doctor’s perception of the huddle will help us understand enablers and barriers to the process and inspire further quality improvements to enhance patient care.

Management of oropharyngeal cancer: a cross-sectional review of institutional practice at a large Canadian referral centre.

BackgroundOver the years, the treatment of oropharyngeal cancer has changed; in the past, first-line treatment consisted of surgery followed by adjuvant radiotherapy, today however, primary treatment typically involves concomitant chemoradiation, and reserves surgery for salvage. While chemoradiation is the modality of choice for primary management of oropharyngeal cancer, disease characteristics, institutional bias, and patient preferences influence treatment choice. This has lead to variation in the treatment of OPC, and has generated some uncertainly regarding the ideal therapeutic approach. The objective of this study was to describe the treatment of OPC a large Canadian referral center, highlighting trends in treatment choice and outcome.MethodsThis is a cross-sectional retrospective review of clinical practice at Sunnybrook Health Science Centre (Toronto, ON). This investigation documents type of first-line treatment, rates of treatment failure, rates of surgical salvage, and 5-year disease-free survival. This study also asses the therapeutic impact of free-flap reconstruction on the use of a postoperative tracheostomy and/or percutaneous endoscopic gastrostomy tube.ResultsThe majority of oropharyngeal cancer patients presented with regionally metastatic disease (stage III-IV) and underwent concomitant chemoradiation as first-line treatment. Just over half of patients who failed chemoradiation were eligible for salvage surgery. Forty-six percent of salvage patients recurred at approximately 6 months, and died approximately 12 months following the first sign of disease recurrence. Five-year survival for salvage patients stage II, III, IVA, and IVB was 100%, 54.5%, 53.8%, and 50%, respectively. The incidence of percutaneous endoscopic gastrostomy tubes and tracheostomies was comparable between patients who underwent free-flap reconstruction and patients who did not.ConclusionThe modality of choice for first-line treatment of oropharyngeal cancer is concomitant chemoradiation. The moderate failure rate following chemoradiation and the modest survival rate following salvage surgery could indicate that selected patients may benefit from undergoing surgery as first-line treatment. While this study did not show that functional outcomes were better for free-flap patients, it is highly likely that those who received a free-flap did better then they would have had they not undergone reconstructive surgery. More research regarding the therapeutic effects of free-flaps in OPC survivors is needed.

A Review of Sun Products and Exposures

Alexis Williams, MD, Dermatology Centre, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada. The author declares no conflicts of interest. Correspondence concerning this article should be addressed to Alexis Williams, MD, University of Toronto, 2075 Bayview Ave., Rm. M1-700, Toronto, Ontario, Canada M4N 3M5. E-mail: [email protected]

Research Highlights

Erin Dahlke, MD, Dermatology Centre, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario. Correspondence concerning this article should be addressed to Erin Dahlke, MD, Dermatology Centre, Sunnybrook Health Science Centre, University of Toronto, Room M1-700, 2075 Bayview Avenue, Toronto, ON M4N 3M5. E-mail: [email protected]

Research Highlights

Jeff Donovan, MD, PhD, Dermatology Centre, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada. Correspondence concerning this article should be addressed to Jeff Donovan, MD, PhD, Dermatology Centre, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Room M1-700, Toronto, Ontario M4N 3M5. E-mail: [email protected]

Three Editorials—Three Historical Allusions

University of Toronto, Sunnybrook Health Science Centre, Toronto, Ontario, Canada. beverley.orser@utoronto.caIn Reply:— I thank Dr. Roy for his thoughtful integration of the three editorials.1–3His broad overview of the evolution of anesthetic practice highlights two important points. As a result of the hard work of our forefathers, we have developed a remarkable understanding of “what anesthetics do.” These insights have produced unprecedented advances in patient safety, primarily as a result of improved monitoring and drug delivery systems. However, we are also reminded that we still don't understand “how anesthetics work.” This lack of knowledge has resulted in a paucity of radically new anesthetic drugs which, in turn, has contributed to a plateau in anesthesia-related mortality.4The specialty of anesthesiology must be ambitious and relentless in its efforts to develop safer anesthetic drugs and improved drug administration strategies. This effort will require a firm commitment to train young investigators who will bring the best science to bear on this important goal.University of Toronto, Sunnybrook Health Science Centre, Toronto, Ontario, Canada. beverley.orser@utoronto.ca

Research Highlights

Jeff Donovan, MD, PhD, Dermatology Centre, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada. Correspondence concerning this article should be addressed to Jeff Donovan, MD, PhD, Dermatology Centre, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Room M1-700, Toronto, Ontario M4N 3M5. E-mail: [email protected]

Multimodal Anesthesia and Systems Neuroscience

Multimodal Anesthesia and Systems Neuroscience

News of The Academy of Neonatal Nursing

This year’s conference lineup is definitely one of our best yet! Just a sampling of evidence-based topics and discussions includes “Proteomics: The Future of Neonatal- Perinatal Medicine,” “Boggy Baby Syndrome,” “Mortality and Morbidity Related to Multiple Births,” and “Cytokines: What Are They and What Do They Do?” Earn an additional 2.5 continuing education credits by signing up for the lunch and breakfast symposiums. The Friday lunch symposium, “How to Interpret a Cochrane Review,” presented by Sharyn Gibbins, PhD, will address a systematic and meaningful approach to interpretation of evidence. Dr. Gibbins is the head of interdisciplinary research and evidence-based practice at the Sunnybrook Health Science Centre in Ontario, Canada. Saturday’s breakfast symposium, “Workforce Issues for Neonatal Nurse Practitioners,” presented by Margaret Steinbach, RN, MSN, ARNP, vice president of advanced practitioners of the Pediatrix Group in Sunrise, Florida, will tackle workforce issues including benefits, salary, and staffing requirements in the face of a nursing shortage. Purchasing tickets for both together saves you $5.

Methodology for evaluating physician order entry (POE) implementations.

The body of physician order entry (POE) implementations literature uses statistical evaluation methods to demonstrate changes in specified variables after POE implementation. To understand and manage the holistic impact of POE on the health care institution, a methodology that utilizes feedback to guide the POE implementation towards the satisfaction of stakeholder objectives is presented. Stakeholders jointly define quantitative and qualitative metrics for their objectives, establish target value vectors for the metrics that represent acceptable implementation outcomes and specify evaluation milestones. These are used to compare pre- and post-POE implementation clinical performance, enabling a socio-technical feedback-improvement cycle. A case study is provided to illustrate how the methodology is being used at Sunnybrook and Women's College Health Science Centre in Toronto, Canada.

A critical examination of the hospital restructuring process in Ontario, Canada

Little work has been done to consider the roles of different forms of knowledge and civil society actors in health policy development. Research on the role of knowledge in policy change has focussed on the contributions of social science knowledge and social scientists. This view assumes that the perspectives and knowledge of experts are the only valid input into the process and is non-critical in its analysis of health policy and health inequities. This paper challenges the reliance upon certain types of knowledge that are brought to bear on the health policy change process, and that knowledge and its creation are impartial activities. This paper presents a conceptual framework of health policy change that incorporates broad concepts of knowledge and civil society actors as contributing to health policy development. It also demonstrates the different dynamics that impinge upon knowledge and its use in health policy change. A case study on hospital restructuring in Toronto, Canada, is presented. Women's College Hospital fought recommended closure and merging of its inpatient services with Sunnybrook Health Science Centre. The case study examined the selection and use of knowledge by the Hospital in building its case against closure.

Evaluation of medical students' performance using the anaesthesia simulator.

A pilot project assessing clinical performance was undertaken using the Anaesthesia Simulation Centre at the University of Toronto. The purpose of this study was to determine the reliability of assessments of medical students' performance using the simulator as an evaluation tool, to compare these assessments to written and clinical evaluations and to elicit student opinion. Simulator assessments were performed at the completion of the anaesthesia rotation. Twenty-four of 177 University of Toronto medical students participated in a videotaped simulator session with an attending faculty. These 24 students were based at Sunnybrook Health Science Centre. During the session, each student worked through one of six predetermined cases involving discrete patient problems based on the list of core objectives. Five evaluators independently assessed each student's videotaped performance using standardized performance evaluation criteria and data were examined for inter-rater reliability. Clinical and written examination marks were compared to simulator assessments. A student questionnaire was administered and descriptive data obtained. The University of Toronto. Medical students. The intraclass correlation coefficient (ICC) of inter-rater reliability was 0.87. There was poor correlation between the simulator and written examination marks (r=0.19, P=0.38) and between the simulator and clinical marks (r=0.04, P=0.87). The simulator experience was highly rated by students: learning experience 4.6 +/- 0.51, appropriate content 4.4 +/- 0.74, use as evaluation tool, 4.1 +/- 0.92 (1=poor, 5=excellent). Our pilot data suggest that the simulator is a reliable assessment method for medical students' performance. Further work may justify the inclusion of the simulator as an evaluation and education tool and expanded to incorporate learning objectives of other medical disciplines.

Cohort Study on Circumcision of Newborn Boys and Subsequent Risk of Urinary-Tract Infection

Population Health Sciences, Research Institute, and Paediatric Outcomes Research Team, Division of Paediatric Medicine, Hospital for Sick Children, Toronto; Institute for Clinical Evaluative Sciences in Ontario, North York; Department of Public Health Sciences, University of Toronto; Clinical Epidemiology Unit, Sunnybrook and Women's College Health Science Centre, North York; and Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada Lancet 1998;352:1813-1816

Critical Care Fellowship Sunnybrook Health Science Centre University of Toronto

Critical Care Fellowship Sunnybrook Health Science Centre University of Toronto

Gender differences in adverse drug reactions.

The objective of this study is to identify gender-related differences in the types of symptoms and drugs reported to cause an adverse drug reaction. Patient data from the Sunnybrook Health Science Centre ADR Clinic for the period from April 1986 to May 1996 were reviewed. Of the 2,367 patients assessed, 74.1% were female. The mean age of the patients was 43 +/- 17 years. Drug classes most frequently reported to elicit an adverse event were general antiinfectives (60.4%), nervous system agents (21.5%), and musculoskeletal agents (3.7%). Skin-related reactions accounted for 49.0% of all reported adverse drug reactions. More than one agent was reported to be responsible for the adverse drug reaction(s) in 50% of the female patients, versus 33.1% of all male patients. Of the female patients, 47.6% were referred for skin or oral challenge testing, versus 41.6% of the male patients. Of the female patients, 6.2% tested positive to the agent compared with 6.1% of all male patients. These results support previous findings that female gender is a risk factor for the development of adverse drug reactions. Further work is required to elucidate the mechanisms explaining the differences observed between male and female patients.

Prostate-specific antigen utilization in Ontario: extent of testing in patients with and without cancer

Objectives: To ascertain the extent of prostate-specific antigen (PSA) testing in patients with prostate cancer (PC), with other cancers (OC), and with no cancer (NC) in two clinical laboratory databases. Design and methods: PSA test records were obtained from a tertiary care hospital, Sunnybrook Health Science Centre (SHSC) and from a private laboratory, Gamma-Dynacare Medical Laboratories (GDL), during the period 1988 to 1995. These records were linked with the Ontario Cancer Registry (OCR) to establish a diagnosis of PC, OC, or NC. Trends in PSA testing according to diagnostic category, testing laboratory, patient age (by decade), and PSA value (in μg/L) were determined. Results: Major cancer sites identified in the patients tested for PSA were prostate (60%), bladder and colon (7% each), lung (5%), kidney (3%), and rectum (3%). There were 11,867 patients (8.5%) with PC, 8,002 (5.9%) with OC, and 118,954 (86%) with NC. The total number of PSA tests performed on these patients was 230,756, of which 21% were on PC, 5% on OC, and 74% on NC; of these tests, 64% were performed through GDL and 36% through SHSC. The mean (median) number of tests per patient was: PC, 4.0 (2); OC, 1.4 (1); and NC, 1.5 (1). For PC 89% and for OC 72% of all tests occurred after diagnosis. Between 1990 and 1995 the number of PSA tests increased two-fold in PC and OC, and 20-fold in NC. We estimate that about one-half of the PSA tests in the NC group were for screening purposes. The proportion of PSA tests occurring in PC, OC, and NC for patients 50 to 70 years of age was 41%, 50%, and 63%, respectively; for patients over 70 years of age, this proportion was 58%, 46%, and 22% respectively; and for patients under 50 it was 1%, 4%, and 15%, respectively. Between 1990 and 1995, the largest increase in testing frequency was in the NC group, particularly in patients 50 to 70 years of age, which was accompanied by a decrease in patients over 70. Less than 10% of testing occurred in patients under 50 in all diagnostic groups. We estimate that about 26% of PSA screening tests in NC occurred outside the guidelines for patient age. Between 1988 and 1995, the proportion of PSA results below our detection limit (<0.2 μg/L) showed a steady rise in the PC group, as did the proportion between 0.2 and 3.9 μg/L; these were accompanied by a fall in the proportion >20.0 μg/L. However, the proportion of PSA results within these ranges did not change much during the same time period for the OC and NC groups. At cutoffs of PSA = 4.0 μg/L (or PSA = 10.0 μg/L), estimates of clinical specificity were 84.0% (or 96.3%), and of clinical sensitivity were 83.4% (or 47.1%). Conclusions: Most (86%) PSA testing occurred in men with NC, consistent with diagnosis or screening. There were more PSA tests per patient in PC than in OC, and most testing occurred after diagnosis. PSA testing in the NC group continues to increase rapidly. The proportion of PSA tests in patients over age 70 decreased in the order of PC > NC > OC. Between 1990 and 1995, there was an increase in the proportion of patients tested who were between 50 and 70 in the NC group, which may suggest more screening in this group. Over this same time period, there was an increase in the proportion of undetectable PSA values, possibly suggesting increased use of radical therapy; there was also a decrease in the proportion of PSA > 20 μg/L, possibly suggesting a decrease in the prevalence of advanced stage PC.